Food Science and Biotechnology

  • 제17권2호
  • /
  • Pages.302-307
  • /
  • 2008
  • /
  • 1226-7708(pISSN)
  • /
  • 2092-6456(eISSN)
한국식품과학회 (Korean Society of Food Science and Technology)
권호 표지

Enzymatic Synthesis of Novel $\alpha$-Amylase Inhibitors via Transglycosylation by Thermotoga maritima Glucosidase

  • Kim, Sung-Hee (Center for Agricultural Biomaterials and Department of Food Science and Biotechnology, School of Agricultural Biotechnology, Seoul National University) ;
  • Lee, Myoung-Hee (Center for Agricultural Biomaterials and Department of Food Science and Biotechnology, School of Agricultural Biotechnology, Seoul National University) ;
  • Yang, Sung-Jae (Center for Agricultural Biomaterials and Department of Food Science and Biotechnology, School of Agricultural Biotechnology, Seoul National University) ;
  • Kim, Jung-Woo (Center for Agricultural Biomaterials and Department of Food Science and Biotechnology, School of Agricultural Biotechnology, Seoul National University) ;
  • Cha, Hyun-Ju (Center for Agricultural Biomaterials and Department of Food Science and Biotechnology, School of Agricultural Biotechnology, Seoul National University) ;
  • Cha, Jae-Ho (Department of Microbiology, Pusan National University) ;
  • Nguyen, Van Dao (Faculty of Biotechnology, Hanoi Open University) ;
  • Park, Kwan-Hwa (Center for Agricultural Biomaterials and Department of Food Science and Biotechnology, School of Agricultural Biotechnology, Seoul National University)
  • 발행 : 2008.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Novel amylase inhibitors were synthesized via transglycosylation by Thermotoga maritima glucosidase (TMG). TMG hydrolyzes acarbose, acarviosine-glucose, and maltooligosaccharide by releasing $^{14}C$-labeled glucose from the reducing end of each molecule. When TMG was incubated with acarviosine-glucose (the donor) and glucose (the acceptor), two major transfer products, compounds 1 and 2, were formed via transglycosylation. The structures of the transfer products were determined using thin-layer chromatography (TLC), high-performance ion chromatography (HPIC), and $^{13}C$ nuclear magnetic resonance (NMR) spectroscopy. The results indicate that acarviosine was transferred to glucose at either C-6, to give a $\alpha-(1{\rightarrow}6$) glycosidic linkage, or at C-3, to produce an $\alpha-(1{\rightarrow}3$) glycosidic linkage. The transfer products showed a mixed-type inhibition against porcine pancreatic $\alpha$-amylase; therefore, they may be useful not only as inhibitors but also as acarbose transition-state analogs to study the mechanism of amylase inhibition.

키워드

참고문헌

  1. Schmidt DD, Frommer W, Junge B, Muller L, Wingender W, Truscheit E, Schafer D. ${\alpha}-Glucosidase$ inhibitors. New complex oligosaccharides of microbial origin. Naturwissenschaften 64: 535-536 (1977) https://doi.org/10.1007/BF00483561
  2. Aleshin AE, Firsov LM, Honzatko RB. Refined structure for the complex of acarbose with glucoamylase from Aspergillus awamori var. X100 to 2.4-A resolution. J. Biol. Chem. 269: 15631-15639 (1994)
  3. Brzozowski AM, Davies GJ. Structure of the Aspergillus oryzae ${\alpha}-amylase$ complexed with the inhibitor acarbose at 2.0A resolution. Biochemistry 36: 10837-10845 (1997) https://doi.org/10.1021/bi970539i
  4. Strokopytov B, Penninga D, Rozeboom HJ, Kalk KH, Dijkhuizen L, Dijkstra BW. X-ray structure of cyclodextrin glycosyltransferase complexed with acarbose. Implications for the catalytic mechanism of glycosidases. Biochemistry 34: 2234-2240 (1995) https://doi.org/10.1021/bi00007a018
  5. Schoffling K, Hillebrand I, Berchtold P. Treatment of diabetes mellitus with the glycoside hydrolase inhibitor acarbose (BAY-g-5421). Front. Horm. Res. 7: 248-257 (1980)
  6. Bischoff H. The mechanism of ${\alpha}-glucosidase$ inhibition in the management of diabetes. Clin. Invest. Med. 18: 303-311 (1995)
  7. Park KH, Kim MJ, Lee HS, Han NS, Kim D, Robyt JF. Transglycosylation reactions of Bacillus stearothermophilus maltogenic amylase with acarbose and various acceptors. Carbohyd. Res. 313: 235-246 (1998) https://doi.org/10.1016/S0008-6215(98)00276-6
  8. Kim M-J, Lee S-B, Lee H-S, Baek J-S, Kim D, Moon T-W, Robyt JF, Park K-H. Comparative study of the inhibition of ${\alpha}-glucosidase$, ${\alpha}-amylase$, and cyclodextrin glucanosyltransferase by acarbose, isoacarbose, and acarviosine-glucose. Arch. Biochem. Biophys. 371: 277-283 (1999) https://doi.org/10.1006/abbi.1999.1423
  9. Lee S-B, Park K-H, Robyt JF. Inhibition of ${\alpha} -glycosidase$ by acarbose analogues containing cellobiose and lactose structures. Carbohyd. Res. 331: 13-18 (2001) https://doi.org/10.1016/S0008-6215(01)00016-7
  10. Baek J-S, Kim J-M, Cha H, Lee H-S, Li D, Kim J-W, Moon T-W, Park K-H. Enhanced transglycosylation activity of Thermus maltogenic amylase in acetone solution. Food Sci. Biotechnol. 12: 639-643 (2003)
  11. Li C, Begum A, Numao S, Park KH, Withers SG, Brayer GD. Acarbose rearrangement mechanism implied by the kinetic and structural analysis of human pancreatic ${\alpha} -amylase$ in complex with analogues and their elongated counterparts. Biochemistry 44: 3347-3357 (2005) https://doi.org/10.1021/bi048334e
  12. Lee M-H, Kim Y-W, Kim T-J, Park C-S, Kim J-W, Moon T-W, Park K-H. A novel amylolytic enzyme from Thermotoga maritima, resembling cyclodextrinase and ${\alpha -glucosidase$ , that liberates glucose from the reducing end of the substrates. Biochem. Bioph. Res. Co. 295: 818-825 (2002) https://doi.org/10.1016/S0006-291X(02)00748-9
  13. Chung MJ, Lee Y-S, Kim B-C, Lee S-B, Moon T-W, Lee S-J, Park K-H. The hypoglycemic effects of acarviosine-glucose modulate hepatic and intestinal glucose transporters in vivo. Food Sci. Biotechnol. 15: 851-855 (2006)
  14. French D, Levin ML, Norberg E, Nordin P, Pazur JH, Wild GM. Studies on the schardinger dextrins. VII. Co-substrate specificity in coupling reactions of Macerans amylase. J. Am. Chem. Soc. 76: 2387-2390 (1954) https://doi.org/10.1021/ja01638a027
  15. Duggleby RG. Regression analysis of nonlinear arrhenius plots: An empirical model and a computer program. Comput. Biol. Med. 14: 447-455 (1984) https://doi.org/10.1016/0010-4825(84)90045-3